The phenotypic effect of some single nucleotide polymorphisms (SNPs) depends on their parental origin. We present a novel approach to detect parent-of-origin effects (POEs) in genome-wide genotype data of unrelated individuals. The method exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups. We applied the method to >56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six lead SNPs were carried forward for replication in five family-based studies (of ∼4,000 trios). Two SNPs replicated: the paternal rs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10 gene) increased BMI equally (beta = 0.11 (SD), P<0.0027) compared to the respective maternal alleles. Real-time PCR experiments of lymphoblastoid cell lines from the CEPH families showed that expression of both genes was dependent on parental origin of the SNPs alleles (P<0.01). Our scheme opens new opportunities to exploit GWAS data of unrelated individuals to identify POEs and demonstrates that they play an important role in adult obesity.

Original publication

DOI

10.1371/journal.pgen.1004508

Type

Journal article

Journal

PLoS Genet

Publication Date

07/2014

Volume

10

Keywords

Adult, Body Mass Index, European Continental Ancestry Group, Female, Gene Expression Regulation, Genetic Predisposition to Disease, Genome-Wide Association Study, Genomic Imprinting, Genotype, Glucose Transport Proteins, Facilitative, Humans, Male, Obesity, Polymorphism, Single Nucleotide, Potassium Channels, Tandem Pore Domain